Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates.

التفاصيل البيبلوغرافية
العنوان: Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates.
المؤلفون: Corbett KS, Werner AP, O' Connell S, Gagne M, Lai L, Moliva JI, Flynn B, Choi A, Koch M, Foulds KE, Andrew SF, Flebbe DR, Lamb E, Nurmukhambetova ST, Provost SJ, Bock KW, Minai M, Nagata BM, Van Ry A, Flinchbaugh Z, Johnston TS, Mokhtari EB, Mudvari P, Henry AR, Laboune F, Chang B, Porto M, Wear J, Alvarado GS, Boyoglu-Barnum S, Todd JM, Bart B, Cook A, Dodson A, Pessaint L, Steingrebe K, Elbashir S, Andersen H, Wu K, Edwards DK, Kar S, Lewis MG, Bortiz E, Moore IN, Carfi A, Suthar MS, McDermott A, Roederer M, Nason MC, Sullivan NJ, Douek DC, Graham BS, Seder RA
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2021 May 24. Date of Electronic Publication: 2021 May 24.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: Background: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351.
Methods: Nonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge.
Results: Eight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID 50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log 10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge.
Conclusions: Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.
تواريخ الأحداث: Date Created: 20210602 Latest Revision: 20220423
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8168383
DOI: 10.1101/2021.05.21.445189
PMID: 34075375
قاعدة البيانات: MEDLINE